Described are methods of treating a subject after acute trauma to the head, viral encephalitis, or other causes of acute neurodegeneration, and/or after acute vascular insults, including ischemic and hemorrhagic strokes, the method comprising administering inhibitors of BACE1 an inhibitory oligonucleotide targeting BACE1 and/or an inhibitory oligonucleotide targeting APLP2. Also described are methods for treating a subject who is at high risk for head trauma, including administering a prophylactically effective amount (i.e., an amount sufficient to reduce the risk of developing or reduce the severity or duration of symptoms of head trauma) of one or more of an inhibitor of BACE1 an inhibitory oligonucleotide targeting BACE1 or an inhibitory oligonucleotide targeting APLP2.